# Inflammation is a driver of newt lens regeneration

> **NIH NIH R21** · MIAMI UNIVERSITY OXFORD · 2022 · $216,750

## Abstract

Newts are one of the closest living relatives to mammals that retain full regenerative capabilities
throughout their entire lifetime. Eguchi et al., demonstrated that the lens of the newt could be
repeatedly removed 18 times over the course of 16 years and the last lens regenerated as
perfectly as the first. This ability in newts is remarkable considering that humans have a high risk
of developing posterior capsule opacification after a single cataract surgery. As a result, we
thought for decades that newts were impervious to fibrotic disease. However, our preliminary data
demonstrates macrophage depletion not only prevented lens regeneration but it also induced a
fibrotic-like response after a single injury in the newt eye. We also found that treatment with the
anti-inflammatory drug dexamethasone prevented lens regeneration but failed to induce a fibrotic
response to injury. This highlights a truly unique role of the newt macrophage in preventing fibrotic
disease. It also suggests that while inflammation and macrophages are necessary for
regeneration in the newt, they have unique functions. Based on our preliminary data and work
done in zebrafish, our hypothesis is that inflammation is required to trigger iris pigmented
epithelial (IPE) cell reprogramming and that macrophages place limits on the inflammatory
potential of the injury site. Thereby the absence of macrophages would be associated with a
fibrotic response to injury resulting from uncontrolled inflammation triggering the recruitment and
differentiation of myofibroblasts and aberrant extracellular matrix deposition. To test these
hypotheses, we will characterize the magnitude and duration of the inflammatory response in the
newt eye, the impact of dexamethasone and macrophage depletion on IPE cell apoptosis,
proliferation, and markers of IPE cell reprogramming. We will also characterize macrophage
polarization states and their transition from M1 to M2 phenotypes during the inflammatory
response. Finally, the type of fibrotic injury induced by macrophage depletion will be further
characterized as well as possible mechanisms leading to its formation. Recent work in mice and
humans has demonstrated an inherent plasticity in macrophage function since they are highly
programmable through manipulation of their local microenvironment. Our long term goal is to
characterize factors in the newt microenvironment that instruct an anti-fibrotic response from newt
macrophages that could be capable of eliciting similar functions in human macrophages as a
treatment or prevention strategy for fibrotic diseases.

## Key facts

- **NIH application ID:** 10433462
- **Project number:** 1R21EY033916-01
- **Recipient organization:** MIAMI UNIVERSITY OXFORD
- **Principal Investigator:** Katia Del Rio-Tsonis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $216,750
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433462

## Citation

> US National Institutes of Health, RePORTER application 10433462, Inflammation is a driver of newt lens regeneration (1R21EY033916-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10433462. Licensed CC0.

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